Packing and mobility of hydrocarbon chains in phospholipid lyotropic liquid crystalline lamellar phases and liposomes: characterisation by positron annihilation lifetime spectroscopy (PALS)

Abstract

Lipid lamellar mesophases and their colloidal dispersions (liposomes) are increasingly being deployed in vivo as drug delivery vehicles, and also as models of biological membranes in fundamental biophysics studies. The permeability and diffusion of small molecules such as drugs is accommodated by a change in local curvature and molecular packing (mesophase behaviour) of the bilayer membrane molecules. Positron annihilation lifetime spectroscopy (PALS) is capable of providing in situ molecular level information on changes in free volume and void space arising from such changes in a non-perturbative manner. In this work PALS was used to systematically characterise the temperature-induced melting transitions (Tm) of saturated and unsaturated phospholipid-water systems while systematically varying lipid chain length, as both bulk lamellar mesophase and as aqueous colloidal dispersions (liposomes). A four-component fit of the data was used that provides separate PALS lifetimes for the aqueous (τ3) and organic domains (τ4). The oPs lifetime (τ4), for the lamellar phases of DSPC (C18:0), DPPC (C16:0), DMPC (C14:0) and DLPC (C12:0) was found to be independent of chain length, with characteristic lifetime value τ4 ∼ 3.4 ns. τ4 is consistently larger in the dispersed liposomes compared to the bulk mesophases, suggesting that the hydrocarbon chains are more mobile. The use of contemporary and consistent analytical approaches as described in this study is the key to future deployment of PALS to interrogate the in situ influence of drugs on membrane and cellular microenvironments.

Application of positron annihilation lifetime spectroscopy (PALS) to study the nanostructure in amphiphile self-assembly materials: phytantriol cubosomes and hexosomes

“…37 In the current work therefore we extend this hypothesis to include other structures and lipids of biophysical and/or pharmaceutical relevance. 37 In the current work therefore we extend this hypothesis to include other structures and lipids of biophysical and/or pharmaceutical relevance.…”

“…11 The sensitivity of PALS to internal nanostructure has been investigated through comparison of oPs and I oPs of both the colloidal dispersions (cubosomes and hexosomes) and ''bulk'' mesophases. 37 Based upon the PALS lifetimes it may be anticipated that the diffusion of hydrophilic moieties from the colloidal dispersions would be more rapid than the ''bulk'' mesophase, which is reasonable given the greater surface area of these as nanoparticles. intravenous vs. depot) and several workers have shown that the nanostructure of the phase impacts upon the release profile of the drug.…”

“…PALS has been used to determine the critical micelle concentration (CMC) of surfactants; [23][24][25][26] to distinguish transformations in micellar geometry [27][28][29][30][31][32] as well as phase transitions in lyotropic liquid crystalline systems [33][34][35][36][37][38] and lipid bilayers. In recent years, positron annihilation lifetime spectroscopy (PALS) has demonstrated its utility as a molecular probe in soft condensed matter systems.…”

Positron annihilation lifetime spectroscopy (PALS): a probe for molecular organisation in self-assembled biomimetic systems

“…42 The overall structures (i.e. itself 56 and/or diffuse from one region to another 3 (Fig. 42,43 Cell membrane morphology is also controlled by the principles of amphiphile self assembly 52,53 and many of the non-lamellar architectures desribed in Fig.…”

“…Dong et al 56 have also compared the sensitivity of the PALS parameters to subtle changes in hydrocarbon packing arising from changes in chain mobility in liposomes, observing that there was no significant difference between the oPs lifetimes of some saturated and unsaturated lipids with C16 (DPPC vs. C 16:1 ) and C18 (DSPC vs. DOPC) chain length. 56 It was proposed that as the hydrophobic chains of the lipids exist in a highly mobile and disordered state within liposomes; this mobility outweighs any effect imposed by saturation.…”